Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Epoxy Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1993

[Supramolecular structure based on protein conjugates with polyalkyleneoxides. Complexes with beta-cyclodextrin].

The reaction of the complex formation between beta-cyclodextrin and alpha-chymotrypsin conjugates with two-component ethylene oxide copolymers with propylene oxide has been described for the first time. The complex formation has been shown to depend on the mode of distribution of the polymer chains in the conjugate. The complex is a crystalline water-insoluble compound; its stoichiometric composition has been determined. The alpha-chymotrypsin conjugate with polyethylene glycol forms a water-soluble complex with beta-cyclodextrin.

Chymotrypsin↗
PubMed1994

Fixation of bioprosthetic tissues with monofunctional and multifunctional polyepoxy compounds.

Collagen from a native tissue is fixed with a polyepoxy compound (PC) for use as a new biologic prosthetic material. Prior studies have shown that this biomaterial has comparable properties with collagen fixed with glutaraldehyde (GA), and thus has great promise for biomedical applications. A prior kinetic study indicated that the reaction between the functional groups of collagen and the multifunctional epoxy EX-313 is a 2.5th-order reaction. The purpose of this study was to understand the mechanism of the amino acid-PC reactions in a fixation process. Bovine arteries were fixed with a monofunctional PC (EX-131) and a multifunctional PC (EX-313) as a function of fixation time. A sequential fixation with a second fixative was used to identify the available remaining reactive sites from a prior fixation. The denaturation temperature (Td) was measured on each sample. Because the denaturation temperature is a direct indication of crosslinking of individual amino acids with the fixative, the increase in Td of a subsequent fixation may be indicative of the available remaining amino acids. The fixation index was measured on each sample to reflect the increase of fixation completion in a sequential fixation process. The fixation index and crosslink data also revealed that the reactive amino acids for EX-131 and EX-313 may not be exactly the same. The data in this study suggest that a monofunctional fixative can pre-react with the amino acids of collagen to effectively block further fixation of collagen with a second fixative. This amino acid masking may be associated with collagen branching. Collagen branching and its effect on denaturation temperature are described.

Animals↗
PubMed1986

Is intercalation a critical factor in the covalent binding of mutagenic and tumorigenic polycyclic aromatic diol epoxides to DNA?

The tumorigenic and mutagenic effects induced by polycyclic aromatic diol epoxides are widely believed to involve the covalent binding of these electrophilic metabolites of polycyclic aromatic hydrocarbons to DNA. Here the relationships between the formation of non-covalent intercalation complexes with DNA, the DNA-catalyzed reaction rates, the formation of tetraols (which constitutes a detoxification pathway) and the level of covalent binding to DNA, are examined critically within the context of available experimental results. When the rates of reaction of the diol epoxide molecules at DNA binding sites dominate over those in the external aqueous solution, the level of covalent binding is independent of the intercalative non-covalent binding (association constant K, M-1) which precedes the covalent binding reaction. However, under conditions in which DNA does not catalyze or enhance the reaction rate of diol epoxide molecules (e.g. at high salt concentrations), or when there are efficient competitive reaction pathways in the solution external to the DNA, the level of covalent binding to DNA is predicted to be directly proportional to K. Since these latter reaction conditions are expected to prevail in a cellular environment, the ability of a given diol epoxide derivative to form intercalative non-covalent complexes with DNA prior to covalent binding should be an important factor in determining the biological activities of these compounds. The experimental conditions which are suitable for testing the relationships between non-covalent intercalative complex formation and covalent binding to DNA in vitro are described.

Binding Sites↗
PubMed2003

Safety of new phosphate binders for chronic renal failure.

Phosphate (Pi) retention is a common problem in patients with chronic kidney disease, particularly in those who have reached end-stage renal disease (ESRD). In addition to causing secondary hyperparathyroidism and renal osteodystrophy, recent evidence suggests that, in ESRD patients, high serum phosphorus concentration and increased calcium and phosphorous (Ca x P) product are associated with vascular and cardiac calcifications and increased mortality. Dietary phosphorus restriction and Pi removal by dialysis are not sufficient to restore Pi homeostasis. Reduction of intestinal Pi absorption with the use of Pi binders is currently the primary treatment for Pi retention in patients with ESRD. The use of large doses of calcium-containing Pi binders along with calcitriol administration may contribute to over-suppression of parathyroid hormone secretion and adynamic bone disease as well as to a high incidence of vascular calcifications. When used in patients with impaired renal function, aluminium salts were found to accumulate in bone and other tissues, resulting in osteomalacia and encephalopathy.Sevelamer, an aluminium- and calcium-free Pi binder can reduce serum phosphorus concentration and is associated with a significantly lower incidence of hypercalcaemia, while maintaining the ability to suppress parathyroid hormone production. An additional benefit of sevelamer is its ability to lower low density lipoprotein-cholesterol and total cholesterol levels. Sevelamer attenuates the progression of vascular calcifications in haemodialysis patients, which may lead to lower mortality. The use of sevelamer in non-dialysed patients might aggravate metabolic acidosis, common in these patients. Several other calcium-free Pi binders are in development. Lanthanum carbonate has shown significant promise in clinical trials in ESRD patients. Magnesium salts do not offer a significant advantage over currently available Pi binders. Their use is restricted to patients receiving dialysis since excess magnesium must be removed by dialysis. Iron-based compounds have shown variable efficacy in short-term clinical trials in small numbers of haemodialysis patients. Mixed metal hydroxyl carbonate compounds have shown efficacy in animals but have not been studied in humans. Major safety issues include absorption of the metal component with possible tissue accumulation and toxicity.

Aluminum↗
PubMed2004

Chiral capillary electrophoresis applied to the determination of phenylglycidol enantiomers obtained from cinnamyl alcohol by asymmetric epoxidation using new titanium(IV) alkoxide compounds as catalysts.

A capillary electrophoresis method for the simultaneous determination of phenylglycidol enantiomers in the presence of an excess of cinnamyl alcohol was developed. The effects of the nature, pH and concentration of the buffer, the nature and concentration of chiral selector, the addition of methanol or acetonitrile, and the capillary temperature on the chiral resolution of phenylglycidol enantiomers were studied. Separations were achieved using 20 mM succinylated beta-cyclodextrin dissolved in a 10 mM borate buffer (pH 10.0). Chiral resolution for the phenylglycidol enantiomers in the optimized electrophoretic conditions was higher than 2.0 with an analysis time less than 7 min. The method developed was validated in terms of selectivity, linearity, precision (instrumental repeatability, method repeatability, intermediate precision), the limits of detection and quantitation, and accuracy. Limits of detection of 6.5 mg/L and 8.3 mg/L for (2S,3S)-(-)-3-phenylglycidol ((S,S)-PG) and (2R,3R)-(+)-3-phenylglycidol ((R,R)-PG), respectively, were obtained. The method was applied to study the asymmetric epoxidation of cinnamyl alcohol with titanium(IV) alkoxide compounds as catalysts in order to evaluate their catalytic activity and stereoselectivity of the epoxidation processes.

Buffers↗
PubMed1984

Metabolic changes in fed rats caused by chronic administration of ethyl 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate, a new hypoglycaemic compound.

Ethyl 2[5(4-chlorophenyl)pentyl]oxirane-2-carboxylate (POCA) is strongly hypoglycaemic in fasted normal and diabetic rats [H. P. O. Wolf, K. Eistetter and G. Ludwig, Diabetologia 22, 456 (1982)]. POCA was fed for 12 weeks to rats on a standard low-fat (3%) diet at levels of 0.05% and 0.2% to give daily intakes of about 50 and 200 mg/per kg body-wt respectively. This is much more than effective hypoglycaemic doses in fasted rats (5-10 mg/kg body-wt). The animals appeared healthy but they had slightly decreased rates of weight gain compared with the controls. POCA caused a 15% increase in the weight of the myocardium and accumulation of lipid in the liver. Chronic administration of POCA did not cause any large changes in water-soluble blood metabolite concentrations, although VLDL-triacylglycerol and both VLDL and HDL cholesterol concentrations were lowered. There were only small changes in some metabolites of the glycolytic and gluconeogenic pathways and the citrate cycle in liver and skeletal muscle. ATP concentrations were maintained in all groups. There were 2- to 3-fold increases in the total content of CoA and of carnitine and their acylated forms. POCA-feeding caused small decreases in LPL activities in heart and had variable effects in adipose tissue. POCA was also fed to a few rats on a high fat (30%) diet for 4 weeks. Only small changes in blood, liver and muscle metabolite concentrations were found, except for large increases in the liver CoA and carnitine contents. It was concluded that POCA does not cause large perturbations of glucose homeostasis, or acute toxic effects, during 12 weeks administration to normal animals at high dose levels. The very-long term importance of accumulation of lipid in liver; increase in myocardial weight; and also of hepatic peroxisomal proliferation [A. J. Bone, H. S. A. Sherratt, D. M. Turnbull and H. Osmundsen, Biochem. biophys. Res. Commun. 104, 708 (1982)] cannot yet be determined. The possible use of POCA and related compounds in the chemotherapy of diabetes merits further investigation.

Animals↗
PubMed1993

The genotoxicity of enantiomeric aliphatic epoxides.

The (R)- and (S)-optical isomers of 9 epoxides, benzyloxymethyloxirane, epichlorohydrin, glycidol, glycidyl 3-nitrobenzenesulfonate, glycidyl 4-nitrobenzoate, glycidyl tosylate, styrene oxide, glycidyl 1-naphthyl ether and glycidyl 4-nitrophenyl ether, have been compared for their in vivo and in vitro genotoxicity. The in vitro short-term test employed was the Ames mutagenicity assay with Salmonella strain TA100. The in vivo tests were chromosomal aberrations (CA) as well as sister-chromatid exchange (SCE) in bone-marrow cells of mice following intraperitoneal administration of these epoxides. Differences in mutagenicity between isomers were established with TA100 for all the compounds. While 13 of the isomers were genotoxic compared to a negative control by CA measurements, only in the case of glycidyl 4-nitrobenzoate could a significant difference be found between isomers by this test. However, with SCE evaluations, differences were detected between the (R)- and (S)-isomers for all the pairs of compounds with the exception of those for benzyloxymethyloxirane and glycidyl 4-nitrophenyl ether. At least in part, differences in the patterns of genotoxicity among compounds can be related to their differences in reaction pathways.

Animals↗
PubMed2001

Total synthesis and antifungal activity of 9-methoxystrobilurin L as the originally proposed 1,4-benzodioxan structure.

Total synthesis of both enantiomers of 9-methoxystrobilurin L as the originally proposed 1,4-benzodioxan structure was successfully achieved. The 1H and 13C NMR spectra of synthesized 9-methoxystrobilurin L were compared with those of a naturally-occurring sample. It was strongly indicated that naturally-occurring 9-methoxystrobilurin L has not the originally reported 1,4-benzodioxan structure but a 1,5-benzodioxepin structure, the same as previously reported 9-methoxystrobilurin K. Antifungal activities of the synthesized compounds toward several typical fungi were also examined, and they were less active than 9-methoxystrobilurin K.

Acrylates↗
PubMed1997

How to starve a tumor.

The formation of new blood vessels, termed angiogenesis, is a central process in the evolution of a tumor and its subsequent metastasis. Angiogenesis is potently inhibited by the fumagillins, a family of epoxide-containing natural products. The recent identification of a protein target for these compounds may help decipher the mechanisms underlying endothelial cell growth. The fact that binding is irreversible may inspire the design of electrophilic inhibitors of other, poorly understood cellular processes.

Aminopeptidases↗
PubMed1984

[In vitro conjugation of allyl alcohol and of its metabolites with reduced glutathione].

Hepatic GSH is utilized in conjugation reactions with the chemically-reactive metabolite, thus its measurement is a useful indication of the extent of conjugation. The toxic effect of allyl alcohol on rat livers is related to its conversion into acrolein. The toxicity of acrolein could be related to further metabolic activation into acrilic acid and/or glycidaldehyde. Allyl alcohol may also be converted into glycidol. Since hepatic GSH is an important determinant of allyl alcohol hepatotoxicity, we have studied "in vitro" reactivity of GSH with allyl alcohol, acrolein and glycidol. The addition of these chemicals to incubation mixtures containing liver 105.000 g supernatant fraction, phosphate buffer and GSH leads to GSH consumption, as measured by the Ellman's method. All the compounds examined react with GSH when added to incubation mixtures containing or no SPM. These results seem to indicate that these chemicals react with glutathione either enzymatically or no.

1-Propanol↗
PubMed1980

Influence of foreign compounds on formation and disposition of reactive metabolites.

Many toxic compounds are unreactive and need biotransformation in order to exert their toxic effects. Several enzymes control the formation or disposition of reactive metabolites. Especially well studied is the group of enzymes responsible for the control of reactive epoxides. Such epoxides may bind spontaneously to DNA, RNA and protein. These alterations of critical cellular macromolecules may disturb the normal biochemistry of the cell and lead to cytotoxic, allergenic, mutagenic and carcinogenic effects. Whether these effects will be manifested depends on the chemical reactivity as well as on other properties (geometry, lipophilicity) of the epoxide in question. Enzymes controlling the concentration of epoxides are another important contributing factor. Several microsomal monooxygenases exist. Some monooxygenases preferentially attack large substrates at single sites, specific for each enzyme. Some of these steps produce reactive metabolites; others are detoxification pathways. Enzymes that metabolize the epoxides represent a further determining factor. These enzymes include epoxide hydrolase (EC 3.3.2.3) and glutathione transferases (EC 2.5.1.18), which do not play a purely inactivating role but can, in some cases, act also as coactivating enzymes. Some of these enzymes have been shown to be influenced by foreign compounds. Acute effects by activation and inhibition of the enzymes as well as long-term effects by induction and repression have been observed. Since different foreign compounds differentially influence various enzymes, they can produce changes not only in overall metabolic activity but also changes in metabolite pattern and in selective toxicities.

Animals↗
PubMed2005

In vitro studies of the influence of certain enzymes on the detoxification of acrylamide and glycidamide in blood.

Several enzymes involved in the metabolism of xenobiotic substances are polymorphic in humans. Inter-individual differences in response to certain chemicals, such as acrylamide, as a result of such genetic polymorphisms might affect health-risk assessments. Detoxification by, for example, conjugation with glutathione (GSH) will decrease the concentration. The dose of the compound and enzymes that enhance the conjugation with GSH will increase the detoxification rate. The dose of acrylamide or glycidamide has been measured in blood samples from individuals with defined genotypes for the glutathione transferases GSTT1 and GSTM1 after in vitro incubation with these compounds. The results indicate that these enzymes have no significant effect on the blood dose, measured as Hb adducts over time, after exposure to acrylamide or glycidamide.

Acrylamide↗
PubMed1978

Mutagenicities of styrene oxide derivatives on Salmonella typhimurium (TA 100): relationship between mutagenic potencies and chemical reactivity.

The lethal and mutagenic effects of p-methyl-, m-chloro-, p-chloro- and unsubstituted styrene oxide on Salmonella typhimurium (TA 100) were investigated. At equal concentrations, p-chlorostyrene oxide was more lethal than p-methyl-, m-chloro- or unsubstituted styrene oxide. When the survival fraction was 0.8 or more, the mutagenicities of these compounds increased in the order: m-chlorostyrene oxide = p-chlorostyrene oxide less than styrene oxide less than p-methyl-styrene oxide. The mutagenicities of these compounds depended only on the reactivity of their benzylic site; the reactivity at their primary site and their partition coefficients appeared to have no effect.

Dose-Response Relationship, Drug↗
PubMed2005

First evidence that cytochrome P450 may catalyze both S-oxidation and epoxidation of thiophene derivatives.

Oxidation of 2-phenylthiophene (2PT) by rat liver microsomes, in the presence of NADPH and glutathione (GSH), led to three kinds of metabolites whose structures were established by 1H NMR and mass spectrometry. The first ones were 2PT-S-oxide dimers formed by Diels-Alder type dimerization of 2PT-S-oxide, while the second ones were GSH adducts derived from the 1,4-Michaël-type addition of GSH to 2PT-S-oxide. The third metabolites were GSH adducts resulting from a nucleophilic attack of GSH to the 4,5-epoxide of 2PT. Oxidation of 2PT by recombinant, human cytochrome P4501A1, in the presence of NADPH and GSH, also led to these three kinds of metabolites. These results provide the first evidence that cytochrome P450 may catalyze the oxidation of thiophene compounds with the simultaneous formation of two reactive intermediates, a thiophene-S-oxide and a thiophene epoxide.

Animals↗
PubMed1999

The coral-derived natural products eleutherobin and sarcodictyins A and B: effects on the assembly of purified tubulin with and without microtubule-associated proteins and binding at the polymer taxoid site.

We examined interactions with purified tubulin of synthetic sarcodictyins A and B and eleutherobin (coral-derived antimitotic agents) and of compound 1, an analogue of sarcodictyin A methylated at the C-3 oxygen atom (i.e., the methyl ketal analogue of sarcodictyin A and thus structurally similar to eleutherobin but lacking the C-3 sugar moiety). Eleutherobin was much more active than sarcodictyins A and B, which were somewhat more active than compound 1. Effects of eleutherobin did not differ greatly from those of paclitaxel and epothilone A. Eleutherobin and epothilone A were competitive inhibitors of the binding of radiolabeled paclitaxel to tubulin polymer (apparent Ki values of 2.1 and 2.6 microM, respectively). Tubulin assembly reactions induced by all compounds were similar to the paclitaxel-driven reactions in being enhanced by the addition of microtubule-associated proteins and/or GTP to the reaction mixture and by progressively higher reaction temperatures. Antiproliferative activity was studied in six human cancer cell lines, including two paclitaxel-resistant lines with point mutations in a beta-tubulin gene. Except for compound 1, effects on cell growth were generally in accord with effects on purified tubulin. Thus, sarcodictyins A and B had IC50 values in the 200-500 nM range; paclitaxel, <10 nM (except in the resistant lines); and eleutherobin and epothilone A, 10-40 nM. The antiproliferative activity of compound 1 was more comparable to that of eleutherobin than sarcodictyin A, despite its weak interaction with tubulin. The activities of the sarcodictyins, eleutherobin, and compound 1 in the mutant ovarian lines were similar to their activities in the parental line.

Alkaloids↗
PubMed1991

DNA adduct formation in liver following the administration of [3H]2-nitrofluorene to rats in vivo.

The formation of RNA and DNA adducts by the environmental pollutant 2-nitrofluorene (2-NF) has been investigated in rat liver in vivo. The adduct pattern was studied after trifluoroacetic acid hydrolysis of DNA or RNA, followed by analysis of the adducts by HPLC. This was also done by enzymatic hydrolysis of DNA, followed by 32P-postlabeling. Both after oral and i.v. administration of [3H]2-NF, one major adduct was found. This adduct did not co-migrate with one of the known adducts of 2-(acetyl)-aminofluorene, N-deoxyguanosin-8-yl-2-aminofluorene (dG-C8-AF), which could have been formed after nitroreduction of 2-NF. 32P-Postlabeling revealed that two minor adducts were also formed, one of which was dG-C8-AF. The observation that the major adduct was also formed after i.v. administration of 2-NF to bile duct-catheterized rats makes a role for the intestinal microflora in the formation of this adduct very unlikely. In vitro experiments with inhibitors of the enzyme epoxide hydrolase indicated that epoxidation of 2-NF may play a role in the microsomal bioactivation of this compound.

2-Acetylaminofluorene↗
PubMed1990

Inhalation pharmacokinetics of 1,3-butadiene and 1,2-epoxybutene-3 in rats and mice.

Studies were conducted on inhalation pharmacokinetics of 1,3-butadiene and of its primary reactive metabolic intermediate 1,2-epoxybutene-3 in rats (Sprague-Dawley) and mice (B6C3F1). Investigations of inhalation pharmacokinetics of 1,3-butadiene revealed saturation kinetics of 1,3-butadiene metabolism in both species. For rats and mice linear pharmacokinetics apply at exposure concentrations below 1000 ppm 1,3-butadiene; saturation of 1,3-butadiene metabolism is observed at atmospheric concentrations of about 2000 ppm. The estimated maximal metabolic elimination rates were 400 mumole/hr/kg for mice and 200 mumole/hr/kg for rats. This shows that 1,3-butadiene is metabolized by mice at about twice the rate of rats. Investigations of inhalation pharmacokinetics of 1,2-epoxybutene-3 revealed major differences in metabolism of this compound between both species. No indication of saturation kinetics of 1,2-epoxybutene-3 metabolism could be observed in rats up to exposure concentrations of 5000 ppm, whereas in mice the saturation of epoxybutene metabolism became apparent at atmospheric concentrations of about 500 ppm. The estimated maximal metabolic rate for 1,2-epoxybutene-3 was 350 mumole/hr/kg in mice and greater than 2600 mumole/hr/kg in rats. When the animals are exposed to high concentrations of 1,3-butadiene, 1,2-epoxybutene-3 is exhaled by rats and mice. For rats 1,2-epoxybutene-3 concentration in the gas phase of the system reaches a plateau at about 4 ppm. For mice, 1,2-epoxybutene-3 concentration increases with exposure time until, at about 10 ppm, signs of acute toxicity are observed. Under these conditions hepatic nonprotein sulfhydryl compounds are virtually depleted in mice but not in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗